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Ann Thorac Surg 1996;62:662-669
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Triiodothyronine Optimizes Sheep Ventriculoarterial Coupling for Work Efficiency

Division of Cardiothoracic Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Triiodothyronine (T₃) administration after cardiopulmonary bypass has been shown to significantly improve cardiac performance. The present study was undertaken to elucidate the effects of T₃, when administered as an intravenous bolus, on both cardiac energetics and stroke work-oxygen utilization (EW/LVVO₂) efficiency.

Methods. In both unstressed and stressed hearts, energetics were evaluated at baseline and 2 hours after intervention in an in vivo sheep preparation. In the first group (n = 5) sheep received saline vehicle. In the second group (n = 9) sheep received an intravenous bolus of 1.2 µg/kg of T₃. In the third group (n = 7) sheep received a 2-hour intravenous infusion of dobutamine at a rate of 5 µg/kg/min.

Results. In the unstressed heart, T₃ improved cardiac function at no cost in oxygen consumption by decreasing afterload and hence improved EW/LVVO₂ efficiency. In contrast, dobutamine improved unstressed cardiac function by increasing contractility at the cost of increased oxygen consumption and thus decreased EW/LVVO₂ efficiency. Triiodothyronine optimized ventriculoarterial coupling for efficiency, but dobutamine optimized coupling for maximal work. In the stressed heart, T₃ again improved EW/LVVO₂ efficiency, but dobutamine had the opposite effect.

Conclusions. The bolus administration of T₃ improves unstressed cardiac performance through optimization of ventriculoarterial coupling for EW/LVVO₂ efficiency, primarily through vasodilation. Triiodothyronine also increases efficiency in the stressed heart. This study supports the use of T₃ in cardiac operations to improve cardiac performance with no cost in oxygen consumption characteristic of inotropic agents.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
See also page 669.

Patients with chronic hyperthyroidism manifest chronotropic and inotropic changes that result in elevated cardiac output and stroke volume and an increased cardiac mass [1]. Because heart rate and contractility are two of the major determinants of myocardial oxygen consumption, one would expect increased oxygen consumption in the hearts of these patients. Increased oxygen consumption has been demonstrated experimentally in papillary muscle from animals with induced chronic hyperthyroidism, and this change has been correlated with increased contractility [2, 3].

Despite these oxygen consumption considerations, intravenous triiodothyronine (T₃) has been used recently in an attempt to treat low cardiac output after operations involving cardiopulmonary bypass [4]. This treatment evolved from the discoveries of a postbypass reduction in the serum levels of total tetraiodothyronine, total T₃, and free T₃ and of a blunted postbypass thyroid-stimulating hormone response to thyrotropin-releasing hormone administration [5–7].

Experimental work has shown that, in postischemic pig, baboon, and rabbit hearts, T₃ supplementation improves the postischemic maximum rate of increase of left ventric- ular pressure (dP/dt), the myocardial adenosine triphosphate concentration, developed pressure, the stroke work-end-diastolic length relationship, and survival [8–10]. However, this work did not investigate the effect of acute intravenous T₃ administration on myocardial oxygen consumption in relation to the beneficial effects found. Recently, Klemperer and colleagues [11] found in an isolated canine heart model that T₃ supplementation increased contractility without increasing myocardial oxygen consumption. Given the known effects of chronic hyperthyroidism on oxygen consumption and oxygen utilization efficiency, one might have expected the acute administration of T₃ to cause a rise in myocardial oxygen consumption as the cost for producing a hemodynamic benefit, in particular for increasing contractility, as occurs with currently available inotropic agents.

We hypothesized that in the in vivo setting T₃ could increase cardiac performance without increasing oxygen consumption by optimizing ventriculoarterial coupling for stroke work-oxygen utilization (EW/LVVO₂) efficiency. To test our hypothesis, we used an in vivo sheep preparation to study energetics and ventriculoarterial coupling after the administration of T₃.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Study Design
Twenty-one healthy Dorsett sheep (weight, 40–50 kg) were studied in compliance with the "Guide for the Care and Use of Laboratory Animals" (NIH publication 85-23, revised 1985). One acute study was performed on each sheep. Sheep were chosen because the left coronary artery in sheep exclusively supplies the left ventricle and septum and there is minimal overlap in the circulations of the two ventricles [12]. Thus, blood flow to the left ventricle and left ventricular oxygen consumption can be quantitated in situ.

Surgical Preparation
Animals were maintained with no oral intake, with the exception of water, the night before operation. After induction with thiopental sodium (25 mg/kg intravenously), all animals were intubated and ventilated with halothane (0.5%–2.0%) and with 100% oxygen at 12 to 20 cycles per minute with a ventilator (Ohio Unitrol V5A ventilator; Airco, Madison, WI). Tidal volumes were adjusted as needed throughout the experiment to keep the animal's pH in the physiologic range (7.38–7.42). Lactated Ringer's solution was administered intravenously throughout the operation to maintain the central venous pressure (CVP) and pulmonary artery wedge pressure at constant values. After intubation the internal jugular and femoral veins and the common carotid and femoral arteries were exposed bilaterally. Leads were placed for electrocardiographic monitoring. A 5F Millar micromanometer-tipped transducer (mode SPC-350; Millar Instruments, Houston, TX) was inserted into the right femoral artery and advanced into the distal abdominal aorta for measurement of peripheral blood pressure. A 10-mL intraaortic impedance balloon (Applied Vascular, Laguna Hills, CA) was inserted into the left femoral artery and advanced into the distal aorta for intermittent partial aortic occlusion. A 5F Millar micromanometer-tipped transducer was placed into the right carotid artery and advanced into the left ventricle for monitoring of left ventricular pressure. A Swan-Ganz pulmonary artery catheter (Edwards Critical Care, Santa Ana, CA) was placed through the right internal jugular for recording of CVP, pulmonary artery wedge pressure, and temperature. A 7F eight-electrode dual-field volumetric conductance catheter (Webster Labs, Baldwin Park, CA) was passed through the left carotid artery and into the left ventricle. Online measurement of intraventricular volume was achieved by connecting the conductance catheter to a Leycom Sigma-5DF signal conditioner-processor (CardioDynamics, Oegstgeest, The Netherlands).

Once catheterization was completed, the animal was turned to the left thoracotomy position. Correct positions of all catheters were verified using fluoroscopy (Siremobil 2; Siemens Medical Systems, Iselin, NJ). A left chest wall resection was performed, including removal of ribs 3 to 6. An umbilical tape snare was placed around the inferior vena cava for intermittent inflow occlusion. A flexible fiberoptic oximetric Swan-Ganz catheter was introduced into the coronary sinus via the accessory hemiazygous vein and positioned in the sinus by palpation for measurement of coronary venous oxygen saturation. The accessory hemiazygos vein was ligated proximal to the catheter insertion site to isolate the coronary sinus blood from the systemic blood. A 20-mm flow probe (Transonic, Ithaca, NY) was placed around the ascending thoracic aorta just distal to the aortic root and posterior to the main pulmonary artery. The left main coronary artery was exposed in the tunnel between the main pulmonary artery and the left atrium, and either a 4- or 6-mm flow probe (Transonic) was placed around the proximal portion of the left main coronary artery.

Experimental Protocol
Animals were divided into three groups. Both baseline and 2-hour postintervention data were collected in each animal. The first group (n = 5) constituted a control group, in which data collection sequences were performed without intervention to demonstrate the stability of the preparation over 2 hours. The second group (n = 9) constituted the T₃ group, in which sheep received an intravenous bolus dose of 1.2 µg/kg of Triostat (liothyronine sodium; SmithKline Beecham Pharmaceuticals, Philadelphia, PA). The third group (n = 7) constituted the dobutamine group, in which a continuous infusion of 5 µg/kg/min of dobutamine was begun after the collection of baseline data and continued for 2 hours through the collection of the 2-hour postintervention data.

In all groups, blood samples were collected before the induction of anesthesia and at 2 hours after treatment for determination of the serum levels of total T₃, free T₃, and reverse T₃ (Nichols Institute, San Juan Capistrano, CA). Total and reverse T₃ levels were determined by radioimmunoassay, and free T₃ levels were determined by tracer dialysis.

All electrical signals were passed through an amplifier (Model 6600; Gould, Cleveland, OH) for signal conditioning. The analog amplifier output was digitized at 200 Hz with a data-acquisition digitizing board (AT-MIO-16H-9; National Instruments, Austin, TX) and routed through an Intel 486DX2-66 MHz microprocessor (Dell, Austin, TX). A custom-designed data-acquisition software program was used to display the data graphically online on a computer monitor and to record the digital data during each 20-second data collection sequence. All measurements were performed with ventilation held at end-expiration.

In unstressed hearts, data were obtained for assessment of unstressed hemodynamics, mechanics, and energetics. In stressed hearts, data were collected only for assessment of energetics over several work loads. After a 10-minute stabilization period following instrumentation, three data collection sequences were performed and their numbers averaged to provide data in the unstressed heart. To calculate the end-systolic elastance (Ees), three data collection sequences were performed while the inferior vena cava snare was snugged to occlude inflow, as previously described [13]. A representative sequence was chosen for the Ees determination.

Once unstressed data were collected, data were obtained at five successively increasing work loads for measurement of the left ventricular oxygen utilization efficiency in the stressed heart. Stress on the left ventricle was transiently increased by inflating the balloon catheter in the descending aorta to varying extents; inflation volumes that produced a 15– to 20–mm Hg rise in the systolic left ventricular pressure from the previous inflation volume were used. A 4-minute stabilization period was allowed at each new work load before data collection.

The details of the volume calibration procedure for the conductance catheter have been previously described [14]. To calibrate the conductance-derived volume signal, we used the method involving the rapid injection of hypertonic saline via the Swan-Ganz catheter to eliminate the parallel conductance of the structures surrounding the left ventricle. The transonic flow probes were calibrated using direct graduated-cylinder measurements of blood flow. Fiberoptic oxygen saturations were calibrated against those obtained from blood analyzed for oxygen saturation in the blood gas laboratory of the Hospital of the University of Pennsylvania. All pressure transducers were calibrated immediately before each experiment and checked for drift during the experiments.

At the conclusion of the 2-hour data collection period, the animal was euthanized, and this consisted of the sequential administration of 50 mg/kg of thiopental sodium given intravenously and 40 mEq of potassium chloride given by intracardiac injection. The heart was excised, and the right atrium, left atrium, and right ventricle were dissected from the left ventricle and weighed. The left ventricle was then weighed separately.

Data Analysis and Theoretical Considerations
Using custom data analysis software, ten consecutive heartbeats were selected from each 20-second data collection sequence and were signal averaged. End-systole and end-diastole were determined, as previously described [15, 16]. Heart rate, CVP, pulmonary artery wedge pressure, and cardiac output (CO) were determined directly from the signal-averaged data. Mean arterial pressure (MAP) was calculated from the signal-averaged systolic and diastolic descending aortic pressures. Stroke volume was calculated from the end-systolic and end-diastolic volumes, as determined by the volume catheter. The systemic vascular resistance (SVR) was calculated by the following equation:

The Ees, a load-independent measure of contractility, was determined from inferior vena cava inflow occlusion data collection sequences, with ten beats chosen per sequence. The Ees was generated from the E_max (the point of maximal pressure divided by volume) values of the pressure-volume loops for the ten chosen beats using a shooting-point numerical iterative method [17]. The left ventricular volume at zero pressure was determined from extrapolation of the Ees line to the volume axis.

Effective arterial elastance (Ea) was calculated using the equation proposed by Sunagawa and associates [18]: Ea = Pes/SV, where Pes is the end-systolic pressure and SV is the stroke volume. On the pressure-volume diagram, Ea is the negative of the magnitude of the slope of the diagonal line connecting the end-systolic pressure-volume point on the pressure-volume trajectory to the point marking end-diastolic volume on the volume axis. The Ea does not represent the elastance of any specific part of the arterial tree, but rather the effective elastance as the ventricle ejects. The coupling between the ventricle and the arterial system (ventriculoarterial coupling) can be assessed by studying the relationship of Ea to Ees. This is important, because for any given state of preload, contractility, and afterload, there is a unique combination of ventricular and arterial elastances that will maximize ventricular stroke work, or external work (EW). The combination that maximizes stroke work occurs when the Ea/Ees ratio is 1.0 [18, 19]. Likewise, there exists a unique Ea/Ees ratio for any given loading and contractile state for which EW/LVVO₂ efficiency is maximized. Mechanical work efficiency is maximized when the Ea/Ees ratio is 0.5 [18, 19]. Ratios outside the range of 0.5 to 1.0 are said to reflect varying degrees of ventricularterial uncoupling as well as changes in the ratio of Ea to ventricular contractility.

External work was calculated using computerized planimetry applied to the signal-averaged pressure-volume loop generated for each data collection sequence. Left ventricular oxygen consumption was calculated as follows:

where CF is the left main coronary arterial flow signal-averaged over ten beats, CaO₂ is the arterial blood oxygen content (mL O₂/dL), CvO₂ is the coronary sinus blood oxygen content (mL O₂/dL), %LV weight is the (LV weight)(100)/(total heart weight), and HR is the heart rate. The oxygen contents in femoral arterial and coronary sinus blood were calculated as follows:

where K is the oxyhemoglobin coefficient for sheep blood and equals 1.35 [20]. In this equation, the plasma oxygen content is ignored. Because the arterial-coronary sinus oxygen content (A-VO₂) reflects the amount of oxygen consumed not only by the left ventricle but also by the rest of the heart, we multiplied the A-VO₂ difference by the %LV weight to estimate the portion of the difference created by the left ventricle.

Statistics
Statistical analysis for comparison of baseline and 2-hour values was performed by computer using SIGMASTAT (Jandel Scientific, San Rafael, CA). Standard tests for normality and paired t tests were performed. Regressions, correlation coefficients, and 95% confidence limits were calculated using SIGMAPLOT (Jandel Scientific). The baseline and 2-hour EW/LVVO₂ regressions for the control, T₃, and dobutamine groups were compared by comparing the baseline and 2-hour slopes for each sheep in each group by paired t test.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Thyroid Hormone Levels
Table 1 lists the thyroid hormone levels obtained in each of the three groups. There was no difference between the baseline and 2-hour values in the control group, demonstrating that the preparation itself did not change the T₃ levels. The baseline values in the T₃ and dobutamine groups were similar to the baseline values in the control group, demonstrating that the status of thyroid function was nearly the same at baseline for all of the sheep used in the study.

Unstressed Hemodynamics
Values for the hemodynamic variables are summarized in Table 2. There was no significant difference in the control group in any of the variables, indicating that the preparation was stable during the 2 hours between data collection time points. In addition, there were no dysrhythmias noted in any of the animals receiving T₃.

The CVP, pulmonary artery wedge pressure, and end-diastolic volume were stable over 2 hours in the control and T₃ groups. The end-diastolic volume in particular is considered an accurate measure of preload [21], and the fact that it did not change in the control group indicates that preload was kept relatively constant throughout the experiment.

Unstressed Left Ventricular and Peripheral Arterial Mechanics and Ventriculoarterial Coupling
The data in Table 3 indicate that T₃ decreased the systemic vascular resistance and hence appeared to function as a vasodilator. Triiodothyronine also decreased the Ea, partially as a result of an increased stroke volume. Although dobutamine is known to have some vasodilating effect, it did not significantly lower the systemic vascular resistance in the concentration used. However, dobutamine did raise the Ea in part by increasing the heart rate, with a resultant decrease in stroke volume. The data in Table 3 indicate that T₃ did not acutely change left ventricular contractility in these unstressed sheep hearts, as measured by either dP/dt or Ees. Dobutamine raised both the dP/dt and the Ees, providing evidence that the lack of change with T₃ administration was not a result of an inability of the model to sense changes in contractility. Moreover, the lack of increase in the T₃ group is not likely a result of deterioration in the preparation because the control group did not show a decrease in contractility over the 2 hours.

Unstressed Left Ventricular Energetics and Efficiency
Figure 1 depicts the changes in left main coronary artery flow, A-VO₂ difference, and LVVO₂ in the different groups. No differences were detected at 2 hours relative to baseline in the control group. Figure 1A shows that both T₃ and dobutamine increased coronary flow (baseline = 168 ± 16.6 versus 2 hours = 219 ± 27.6 mL/100 g • min for T₃; baseline = 176 ± 15.1 versus 2 hours = 390 ± 21.2 mL/100 g • min for dobutamine) (mean ± standard deviation; p < 0.01 for both groups). However, Figure 1B shows that the A-VO₂ difference was decreased by T₃. Hence, T₃ significantly decreased oxygen consumption (Fig 1C) in the unstressed state by a combination of primary coronary artery dilatation and decreased cardiac oxygen extraction (LVVO₂ at baseline = 58.6 ± 4.4 versus LVVO₂ at 2 hours = 49.8 ± 3.3 µL O₂/100 g • beat for T₃) (mean ± standard deviation; p < 0.01 for both groups). Dobutamine, however, increased unstressed oxygen consumption, reflecting the increased stroke work performed by the ventricle and the need for increased coronary flow and oxygen extraction (LVVO₂ at baseline = 61.3 ± 9.0 versus LVVO₂ at 2 hours = 95.3 ± 7.0 µL O₂/100 g • beat for dobutamine) (mean ± standard deviation; p < 0.01 for both groups).

View larger version (30K): [in this window] [in a new window]   Fig 1. . (A) Unstressed left main coronary artery flow for the control, triiodothyronine (T3), and dobutamine groups. (B) Arterial-coronary sinus oxygen content (A-VO2) difference for the groups. (C) Left ventricular oxygen consumption (LVVO2) for the groups. Bar diagrams demonstrate the mean and the standard error of the mean for the baseline (B) and 2-hour (2HR) treatment time points for each group. All values are normalized to 100 g of left ventricle. (* = p < 0.01 for paired t test, comparing baseline and 2-hour values.)

View larger version (46K): [in this window] [in a new window]   Fig 2. . Regressions of left ventricular oxygen consumption (LVVO2) on external mechanical work (EW) over several different left ventricular work loads. Baseline and 2-hour postintervention data are presented for each group. All baseline data and the control group 2-hour data are regressed together. The triiodothyronine (T3) and dobutamine 2-hour regression slopes are significantly different from their respective baseline regression slopes (p < 0.01 for both). The linear equations describing the combined baseline and 2-hour control regression and the 2-hour T3 and dobutamine regressions are shown in the box. Values are expressed per 100 g of left ventricle. The 95% confidence limits are indicated for each regression.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

Hesitation to use intravenous T₃ in the clinical setting after cardiac operations may originate from fear that the drug will produce acute hyperthyroidism and hence increase the work load and oxygen consumption of an already injured heart. We found that the intravenous administration of doses of T₃ that produce serum levels consistent with hyperthyroidism did not acutely increase the work load of the unstressed heart but did acutely increase coronary and systemic blood flow. In addition, ventricular oxygen consumption was decreased in the unstressed heart, resulting in an overall increased EW/LVVO₂ efficiency.

Our peripheral arterial mechanics analysis revealed improved forward flow and decreased systemic vascular resistance and Ea in response to T₃. These findings support an acute cardiac unloading effect of intravenous T₃. Triiodothyronine causes relaxation of rat aortic smooth muscle cells in vitro, and this action appears to occur by a pathway independent of ß-receptors [22]. One possible mechanism involves the sarcoplasmic reticulum (SR) Ca²⁺-adenosinetriphosphatase (ATPase). In physiologic concentrations, T₃ and tetraiodothyronine stimulate the SR Ca²⁺-ATPase in striated muscle by an extranuclear mechanism [23]. Because the SR Ca²⁺-ATPase is involved in the regulation of the intracytoplasmic Ca²⁺ concentration and hence vascular smooth muscle contraction and relaxation, stimulation by T₃ may cause sequestration of Ca²⁺ and hence vascular relaxation through SR Ca²⁺-ATPase stimulation.

The idea that the effects of T₃ on the heart cannot be separated from its effects on the entire cardiovascular system led us to study T₃ using the sheep in vivo preparation in which ventriculoarterial coupling could be measured. We found that a decrease in the Ea/Ees ratio toward 0.5 with T₃ administration resulted in better EW/LVVO₂ efficiency. Decreasing afterload with nitroprusside administration in humans has also been found to decrease the Ea/Ees ratio toward 0.5 [24]. Hence, we found that the mechanics and energetics in the unstressed heart are improved by T₃ through a vasodilating mechanism, as occurs with nitroprusside. Additional evidence for an afterload-reducing effect of intravenously administered T₃ has recently been provided by Klemperer and associates [25]. In their prospective randomized clinical trial, elevating the decreased postbypass T₃ levels in patients with low preoperative ejection fractions was found to increase cardiac output and lower systemic vascular resistance. These findings in humans are in agreement with the present findings in sheep.

Additional support for the supplementation of low postbypass T₃ levels has recently been provided by Klemperer and colleagues [11]. In an ex vivo canine heart preparation, they found that supplementing low postischemic T₃ levels improved preload-recruitable stroke work, an index of myocardial contractility, without altering the myocardial oxygen consumption-pressure-volume area relationship. They also found increased coronary flow with T₃ supplementation. Importantly, they found no increase in the preload-recruitable stroke work index in nonischemic hearts with T₃ administration. These results agree with ours, because we also did not appreciate an increase in measures of ventricular contractility (dP/dt or Ees) in our nonischemic hearts, even with the highly elevated total and free T₃ levels we were able to achieve. In addition, we also observed an increase in coronary flow. Although their preparation did not permit analysis of ventriculoarterial coupling, their finding that ventricular oxygen consumption was not increased by T₃ administration was in agreement with our findings. The increase in contractility seen in their postischemic hearts may reflect differing effects of T₃ on the normal and postischemic injured heart. The effects of T₃ on ventriculoarterial coupling in the postischemic heart remain to be studied, but taken together, our results and those of Klemperer and colleagues indicate that there may be both a contractility benefit and a ventriculoarterial coupling benefit that may combine in the postischemic heart to greatly increase forward flow without the increased oxygen cost characteristic of currently available inotropic agents. This potential contractility benefit without oxygen cost in combination with a peripheral vasodilating effect may point up a benefit of T₃ over conventional pharmacologic cardiac support.

In summary, intravenously administered T₃ acutely increased cardiac output, unstressed EW/LVVO₂ efficiency, and EW/LVVO₂ efficiency at progressively increasing work loads by optimizing ventriculoarterial coupling, primarily through a systemic vasodilating mechanism. These data support the supplementation of low T₃ levels in the setting of cardiac operations.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
We gratefully acknowledge SmithKline Beecham Pharmaceuticals for donating the Triostat used in these experiments. We also gratefully acknowledge Randy Rossi, Angela M. DiPierro, RN, and Vincent J. Fausto, Jr, for assistance with the preparation.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Presented at the Poster Session of the Thirty-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29–31, 1996.

Address reprint requests to Dr Gardner, Division of Cardiothoracic Surgery, Hospital of the University of Pennsylvania, 4th Fl Silverstein Bldg, 3400 Spruce St, Philadelphia, PA 19104-4283.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Klein I. Thyroid hormone and the cardiovascular system. Am J Med 1990;88:631–7.[Medline]
2. Skelton CL, Coleman HN, Wildenthal K, Braunwald E. Augmentation of myocardial oxygen consumption in hyperthyroid cats. Circ Res 1970;27:301–9.[Abstract/Free Full Text]
3. Gunning JF, Harrison CE Jr, Coleman HN. Myocardial contractility and energetics following treatment with d-thyroxine. Am J Physiol 1974;226:1166–71.[Free Full Text]
4. Novitzky D, Cooper DKC, Barton CI, et al. Triiodothyronine as an inotropic agent after open heart surgery. J Thorac Cardiovasc Surg 1989;98:972–8.[Abstract]
5. Bremner WF, Taylor KM, Baird S. Hypothalamo-pituitary-thyroid axis function during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1978;75:392–9.[Abstract]
6. Robuschi G, Medici D, Fesani F, et al. Cardiopulmonary bypass: "a low T4 and T3 syndrome" with blunted thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH). Hormone Res 1986;23:151–8.[Medline]
7. Holland FW, Brown PS Jr, Weintraub BD, Clark RE. Cardiopulmonary bypass and thyroid function: a "euthyroid sick syndrome." Ann Thorac Surg 1991;52:46–50.[Abstract]
8. Novitzky D, Human PA, Cooper DKC. Inotropic effect of triiodothyronine following myocardial ischemia and cardiopulmonary bypass: an experimental study in pigs. Ann Thorac Surg 1988;45:50–5.[Abstract]
9. Novitzky D, Human PA, Cooper DKC. Effect of triiodothyronine (T3) on myocardial high energy phosphates and lactate after ischemia and cardiopulmonary bypass: an experimental study in baboons. J Thorac Cardiovasc Surg 1988;96:600–7.
10. Wechsler AS, Kadletz M, Ding M, Abd-Elfattah A, Dyke C. Effects of triiodothyronine on stunned myocardium. J Card Surg 1993;8(Suppl):338–41.[Medline]
11. Klemperer JD, Zelano J, Helm RE, et al. Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia. J Thorac Cardiovasc Surg 1995;109:457–65.[Abstract/Free Full Text]
12. Markovitz LJ, Savage EB, Ratcliffe MB, et al. Large animal model of left ventricular aneurysm. Ann Thorac Surg 1989;48:838–45.[Abstract]
13. Kass DA, Yamazaki T, Burkhoff D, Maughan WL, Sagawa K. Determination of left-ventricular end-systolic pressure-volume relationships by the conductance (volume) catheter technique. Circulation 1986;73:586–95.[Abstract/Free Full Text]
14. Baan J, van der Velde ET, de Bruin HG, et al. Continuous measurement of left ventricular volume in animals and humans by conductance catheter. Circulation 1984;70:812–23.[Abstract/Free Full Text]
15. Sagawa K, Maughan L, Suga H, Sunagawa K. Cardiac contraction and the pressure-volume relationship. New York: Oxford University Press, 1988:302.
16. Ratcliffe MB, Bavaria JE, Wenger RK, Bogen DK, Edmunds LH Jr. Left ventricular mechanics of ejecting, postischemic hearts during left ventricular circulatory assistance. J Thorac Cardiovasc Surg1011991245–55.[Abstract]
17. Kono A, Maughan WL, Sunagawa K, Hamilton K, Sagawa K, Weisfeldt ML. The use of left ventricular end-ejection pressure and peak pressure in the estimation of the end-systolic pressure-volume relationship. Circulation 1984;70:1057–65.[Abstract/Free Full Text]
18. Sunagawa K, Maughan WL, Sagawa K. Optimal arterial resistance for the maximal stroke work studied in isolated canine left ventricle. Circ Res 1985;56:586–95.[Abstract/Free Full Text]
19. Burkhoff D, Sagawa K. Ventricular efficiency predicted by an analytical model. Am J Physiol 1986;250 (Regulatory Integrative Comp Physiol 19):R1021–7.[Abstract/Free Full Text]
20. Bishop DW, Brown FA Jr, Jahn TL, Prosser CL, Wulff VJ. Comparative animal physiology. Philadelphia: Saunders, 1950:316.
21. Kass DA. Clinical ventricular pathophysiology: a pressure-volume view. In: Warltier DC, ed. Ventricular function. Baltimore: Williams & Wilkins, 1995, 131–51.
22. Ojamaa K, Balkman C, Klein IL. Acute effects of triiodothyronine on arterial smooth muscle cells. Ann Thorac Surg 1993;56:S61–7.
23. Warnick PR, Davis FB, Cody V, Davis PJ, Blas SD. Stimulation in vitro of rabbit skeletal muscle sarcoplasmic reticulum Ca²⁺-ATPase activity by thyroid hormone and bipyridines. In: Proceedings of the 70th Annual Meeting of The Endocrine Society, New Orleans, LA, 1988:abstract 356.
24. Starling MR. Left ventricular-arterial coupling relations in the normal human heart. Am Heart J 1993;125:1659–66.[Medline]
25. Klemperer JD, Klein I, Gomez M, et al. Thyroid hormone treatment after coronary-artery bypass surgery. N Engl J Med 1995;333:1522–7.[Abstract/Free Full Text]

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				R. D. Mainwaring, E. Capparelli, K. Schell, M. Acosta, and J. C. Nelson Pharmacokinetic Evaluation of Triiodothyronine Supplementation in Children After Modified Fontan Procedure Circulation, March 28, 2000; 101(12): 1423 - 1429. [Abstract] [Full Text] [PDF]

				N. Murai, Y. Katayama, T. Yamada, T. Imazeki, Y. Irie, H. Kiyama, Y. Sato, I. Hata, H. Yoshida, and M. Mukouyama Thyroid Hormone and Myocardial Metabolism After Heart Surgery in Dogs Asian Cardiovasc Thorac Ann, March 1, 1999; 7(1): 13 - 17. [Abstract] [Full Text] [PDF]

				G. E. Cimochowski, M. D. Harostock, and P. J. Foldes MINIMAL OPERATIVE MORTALITY IN PATIENTS UNDERGOING CORONARY ARTERY BYPASS WITH SIGNIFICANT LEFT VENTRICULAR DYSFUNCTION BY MAXIMIZATION OF METABOLIC AND MECHANICAL SUPPORT J. Thorac. Cardiovasc. Surg., April 1, 1997; 113(4): 655 - 666. [Abstract] [Full Text]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Francis V. DiPierro Joseph E. Bavaria David J. Polidori Michael A. Acker Timothy J. Gardner Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DiPierro, F. V. Articles by Gardner, T. J. Search for Related Content PubMed PubMed Citation Articles by DiPierro, F. V. Articles by Gardner, T. J.